Developing Chinese race-specific warfarin dose prediction algorithms

Int J Clin Pharm. 2023 Jun;45(3):731-738. doi: 10.1007/s11096-023-01565-1. Epub 2023 Mar 29.

Abstract

Background: Numerous genotype-guided warfarin dosing algorithms have been developed to individualize warfarin doses, but they can only explain 47-52% of the variability.

Aim: This study aimed to develop new warfarin algorithms suitable to predict the stable warfarin dose for the Chinese population and to compare their prediction performance with those of the most commonly used algorithms.

Method: Multiple linear regression analysis with the warfarin optimal dose (WOD), logarithm (log) WOD, 1/WOD, and [Formula: see text], respectively, as the dependent variables were performed to deduce a new warfarin algorithm (NEW-Warfarin). WOD was the stable dose that maintained the international normalized ratio (INR) within the target range (2.0-3.0). Three major genotype-guided warfarin dosing algorithms were selected and compared against NEW-Warfarin predictive performance using the mean absolute error (MAE). Furthermore, patients were divided into five groups according to warfarin indications [atrial fibrillation (AF), pulmonary embolism (PE), cardiac-related disease (CRD), deep vein thrombosis (DVT), and other diseases (OD)]. Multiple linear regression analyses were also performed for each group.

Results: The regression equation with [Formula: see text] as the dependent variable had the highest coefficient of determination (R2 = 0.489). The NEW-Warfarin had the best predictive accuracy compared to the three algorithms selected. Group analysis, according to indications, showed that the R2 of the five groups were PE (0.902) > DVT (0.608) > CRD (0.569) > OD (0.436) > AF (0.424).

Conclusion: Dosing algorithms based on warfarin indications are more suitable for predicting warfarin doses. Our research provides a novel strategy to develop indication-specific warfarin dosing algorithms to improve the efficacy and safety of warfarin prescribing.

Keywords: Clinical factors; Dose prediction algorithm; Indications; Pharmacogenomics; Predictive accuracy; Warfarin.

MeSH terms

  • Algorithms
  • Anticoagulants
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Cytochrome P-450 CYP2C9 / genetics
  • East Asian People
  • Genotype
  • Humans
  • International Normalized Ratio
  • Pharmacogenetics
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin* / administration & dosage

Substances

  • Anticoagulants
  • Cytochrome P-450 CYP2C9
  • Vitamin K Epoxide Reductases
  • Warfarin